RRM1在晚期非小细胞肺癌患者外周血中的表达及其对吉西他滨化疗预后的意义

RRM1 Gene Expression in Peripheral Blood in Relation to the Prognosis of Advanced Non-Small Cell Lung Cancer Treated with Gemcitabine

目的探讨外周血与肿瘤组织中核苷酸还原酶M1(ribonucleotide reductase M1,RRM1)表达的相关性,并进一步分析其与吉西他滨联合铂类治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)预后的相关意义。方法通过荧光实时定量PCR检测34例NSCLC患者外周血中RRM1 mRNA表达水平,并与患者的组织病理学类型、临床分期及吉西他滨联合铂类化疗方案疗效的关系进行分析。同时进一步对外周血和肿瘤组织中RRM1 mRNA表达水平的相关性进行分析研究。结果外周血中的RRM1 mRNA在不同的临床分期(ⅢB和Ⅳ)和组织病理学类型(鳞癌、腺癌)中表达均无差异;在与肿瘤化疗反应相关性分析中发现,RRM1低表达组有效率(52.9%)、高于高表达组(5.9%)(P<0.05)。同时,在对生存期的分析中发现RRM1低表达组的生存期(15.5月)明显长于高表达组(11.8月)(P<0.05)。且外周血中RRM1 mRNA的表达与肿瘤组织中呈线性相关(P=0.004)。结论外周血中RRM1低表达的NSCLC患者对吉西他滨化疗反应的有效率更高,生存期更长,其将有助于遴选适合接受吉西他滨联合铂类一线化疗方案的患者。

OBJECTIVE To investigate the clinical prognostic significance of ribonucleotide reductase M1（RRM1） gene expression in peripheral blood of Chinese patients with non-small-cell lung cancer（NSCLC） treated with gemcitabine.METHODS Peripheral blood obtained from 34 Chinese patients with advanced NSCLC was collected to investigate the expression level of RRM1 by real-time PCR（including 24 tissue samples）.Relationships between the gene expression and the overall survival time of patients with NSCLC were analyzed by using Kaplan-Meier survival curve and the log-rank test.The relationship of RRM1 gene expression between peripheral blood and tissue samples were also analyzed by Spearman correlation analysis.RESULTS The expression of RRM1 mRNA had no significance difference between clinical stage ⅢB and Ⅳ of NSCLC,and between Squamous cell carcinoma and Adenocarcinoma of NSCLC.Efficient rates were 52.9%（9/17） in patients with low RRM1 expression level and 5.9%（1/17） in patients with high RRM1 expression level（P0.05）.Moreover,the survival time of patients with low RRM1 expression levels in peripheral blood was significantly longer than that of patients with high RRM1 expression levels（15.5 months vs 11.8 months,P0.05）.Meanwhile,the expression of RRM1 in peripheral blood and tissue in 24 Chinese NSCLC patients showed a correlation（P=0.004） by the Spearman′s rank correlation method.CONCLUSION The patients with low RRM1 expression levels in peripheral blood had higher response to chemotherapy and longer survival time.The results of this study may be helpful for selecting patients of advanced non-small cell lung cancer with low RRM1 expression levels to accept gemcitabine combined with platinum.